Implantable
devices are versatile and promising drug delivery systems,
and their advantages are well established. Of these advantages, long-acting
drug delivery is perhaps the most valuable. Hydrophilic compounds
are particularly difficult to deliver for prolonged times. This work
investigates the use of poly(caprolactone) (PCL)-based implant
coatings as a novel strategy to prolong the delivery of hydrophilic
compounds from implantable devices that have been prepared by additive
manufacturing (AM). Hollow implants were prepared from poly(lactic
acid) (PLA) and poly(vinyl alcohol) (PVA) using fused filament fabrication
(FFF) AM and subsequently coated in a PCL-based coating. Coatings
were prepared by solution-casting mixtures of differing molecular
weights of PCL and poly(ethylene glycol) (PEG). Increasing the proportion
of low-molecular-weight PCL up to 60% in the formulations decreased
the crystallinity by over 20%, melting temperature by over 4 °C,
and water contact angle by over 40°, resulting in an increased
degradation rate when compared to pure high-molecular-weight PCL.
Addition of 30% PEG to the formulation increased the porosity of the
formulation by over 50% when compared to an equivalent PCL-only formulation.
These implants demonstrated
in vitro
release rates
for hydrophilic model compounds (methylene blue and ibuprofen sodium)
ranging from 0.01 to 34.09 mg/day, depending on the drug used. The
versatility of the devices produced in this work and the range of
release rates achievable show great potential. Implants could be specifically
developed in order to match the specific release rate required for
a number of drugs for a wide range of conditions.
Methicillin-resistant Staphylococcus aureus (MRSA) can cause harmful and
potentially deadly infections. Vancomycin
remains the first-line antibiotic treatment for MRSA-derived infections.
Nevertheless, as a peptide drug, it is poorly absorbed when administered
orally because of its high molecular weight and low permeability in
the gastrointestinal tract and is therefore administered intravenously
for the treatment of systemic diseases. In order to circumvent some
of the many drawbacks associated with intravenous injection, other
routes of drug delivery should be investigated. One of the strategies
which has been employed to enhance transdermal drug delivery is based
on microarray patches (MAPs). This work, for the first time, describes
successful transdermal delivery of vancomycin hydrochloride (VCL)
using dissolving MAPs (DMAPs) and hydrogel-forming MAPs (HFMAPs).
VCL was formulated into DMAPs and reservoirs [film dosage forms, lyophilized
wafers, and compressed tablets (CSTs)] using excipients such as poly(vinyl
pyrrolidone), poly(vinyl alcohol), sodium hyaluronate, d-sorbitol,
and glycerol. In this study, HFMAPs were manufactured using aqueous
blends containing poly(methylvinyl ether-co-maleic
acid) cross-linked by esterification with poly(ethylene glycol). The
VCL-loaded CSTs (60% w/w VCL) were the most promising reservoirs to
be integrated with HFMAPs based on the physicochemical evaluations
performed. Both HFMAPs and DMAPs successfully delivered VCL in ex vivo studies with the percentage of drug that permeated
across the neonatal porcine skin recorded at 46.39 ± 8.04 and
7.99 ± 0.98%, respectively. In in vivo studies,
the area under the plasma concentration time curve from time zero
to infinity (AUC0–∞) values of 162.04 ±
61.84 and 61.01 ± 28.50 μg h/mL were achieved following
the application of HFMAPs and DMAPs, respectively. In comparison,
the AUC0–∞ of HFMAPs was significantly greater
than that of the oral administration control group, which showed an
AUC0–∞ of 30.50 ± 9.18 μg h/mL
(p < 0.05). This work demonstrates that transdermal
delivery of VCL is feasible using DMAPs and HFMAPs and could prove
effective in the treatment of infectious diseases caused by MRSA,
such as skin and soft tissue infections, lymphatic-related infections,
and neonatal sepsis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.